The invention relates to the use of tris(trifluoromethylsulfonyl)methane and its alkali metal salts and alkaline earth metal salts as catalysts in the reaction of Lewis-acid-activatable or Brxc3x6nsted-acid-activatable electrophiles with nucleophiles or for carrying out [4+2]-cycloadditions, and to the provision of the novel Mg salt of tris(trifluoromethylsulfonyl)methane.
The Lewis-acid-induced reaction of electrophiles, for example alkyl chlorides or carbonyl compounds, with nucleophiles is a simple, widely used and long-known synthesis method for building up carbon skeletons.
The metal halides MXn used here as Lewis acids, for example TiCl4, ZnCl2 or AlCl3 are frequently, as in the case of Friedel-Crafts acylations, used in equimolar amounts and must be irreversibly deactivated by hydrolysis during the work-up of the reaction batches. This produces large amounts of unutilizable wastes. However, carrying out industrial-scale syntheses in which unutilizable byproducts are formed is highly problematical from the ecological and economic aspects. Reutilizable Lewis acid systems and their use in Lewis-acid-induced carbon-carbon bond formations is, if possible, to be given preference.
Reusable Lewis acid systems in carbon-carbon bond-forming syntheses are, for example, lithium perchlorate or magnesium perchlorate in strongly coordinating organic solvents, such as diethyl ether, or in non-coordinating solvents, such as dichloromethane.
In this case the solutions of lithium perchlorate or magnesium perchlorate in diethyl ether show a sufficient ionization capacity in order to partially ionize, for example trityl chloride, in order to achieve the desired reaction, the ionization capacity increasing with increasing lithium salt concentration (cf. Y. Pocker, R. F. Buchholz, J. Am. Chem. Soc. 1970, 92, 2075-2084). The strong coordinating interaction between the lithium cation and the solvent diethyl ether favour, however, the formation of etherates and therefore decrease considerably the Lewis acidity of the lithium cation (Y. Pocker et al., loc. cit.). Therefore, the pronounced Lewis acid properties of lithium perchlorate solutions are restricted in ether to highly concentrated solutions. Such solutions are used, in particular, in the catalysis of Diels-Alder reactions with substances sensitive to hydrolysis, in which case as an additional effect the formation of the endo-cycloadducts is promoted.
Although the solubility of lithium perchlorate in non-coordinating solvents such as dichloromethane is very low (solubility  less than  less than 10xe2x88x923 mol/l), a suspension of lithium perchlorate in dichloromethane also has Lewis acid properties. Aldehydes are sufficiently activated in this heterogeneous medium, for example, for reactions with 1-tert-butyldimethylsiloxy-1-methoxyethene to give the corresponding xcex2-siloxycarboxylic esters (Mukaiyama-aldol reaction), in which case lithium perchlorate is used in catalytic amounts with respect to the starting materials.
However, the use of lithium perchlorate and magnesium perchlorate as Lewis acids in the organic synthesis is a considerable hazard potential, which is due firstly to the redox instability of the perchlorates (risk of decomposition and explosion) and secondly to the formation of organic perchlorates which cannot be safely excluded in the reaction to be catalyzed (P. G. Urben, Chemtech 1991 (5), 259; A. B. Charette in Encyclopedia of Reagents for Organic Synthesis (Edited by L. A. Paquette), J. Wiley and Sons, New York 1995, Vol. 5, p. 3155). The use of perchlorates as Lewis acids in industrial synthesis is therefore a problem. Although it is possible to recover lithium perchlorate or magnesium perchlorate from the organic reaction solvents, such as ether, dichloromethane or pentane, in principle by aqueous extraction, the crystallization of the perchlorates from water is in turn associated with the above-described risks and also with a high energy consumption, so that the work-up is unfavourable for safety and economic reasons.
The object therefore underlying the present invention is to provide Lewis acid catalysts for the reaction of electrophiles with nucleophiles, which catalysts can be used safely industrially and can be recovered readily and safely without a high energy consumption.
This object is achieved by using at least one compound of formula (1)
M+x[C(SO2CF3)3]xxe2x80x83xe2x80x83(1)
where x is 1 or 2,
M is a hydrogen atom or alkali metal atom when x is 1, or an
alkaline earth metal atom when x is 2, as catalyst.
The preparation of tris(trifluoromethylsulfonyl)methane and also of certain alkali metal and alkaline earth metal tris(trifluoromethylsulfonyl)methanides of the formula (1) is known and described in L. Turowski, K. Seppelt, Inorg. Chem. 1988, 27, 2135-2137; K. Seppelt, Angew. Chem. 1993, 105, 1074-1076 and in J. Org. Chem. Vol. 38, No. 19, pages 3358 ff. Tris(trifluoromethylsulfonyl)methane and its lithium salt and potassium salt are also disclosed by (Beilstein Registry Nos. 4767561, 5899593,. WO 92/FR1024).
The compounds of the formula (1) may, because of their low solubility in non-coordinating solvents, be removed simply by filtration from the reaction batches. Since the compounds of the formula (1) are distinguished by high redox stability and thermal stability, syntheses using these salts and their recovery from the reaction batches have a markedly lower hazard potential than analogous reactions using inorganic perchlorates.
The compound of the formula (1) preferably used is the acid itself (M=H), the lithium, potassium, magnesium or calcium salts, and in particular the lithium and magnesium salts.
The compounds of the formula (1) are used in homogeneous solution in a coordinating organic solvent, for example diethyl ether, THF or dioxane. The concentration of the compound (1) is in this case in catalytic amounts, preferably in the range from 0.01 to 0.1 mol/l, in particular 0.02-0.04 mol/l.
It is also possible to use the compounds of the formula (1) as a suspension in non-coordinating organic solvents, for example dichloromethane, chloroform, carbon tetrachloride or hydrocarbons, such as n-hexane, n-pentane, preferably dichloromethane.
Based on electrophile, 0.01-10 mol %, preferably 0.5-6 mol %, of a compound of the formula (1) can be used.
Using the compounds of the formula (1), Lewis-acid-induced or Brxc3x6nsted-acid-induced carbon-carbon bond-forming syntheses and [4+2] cycloadditions of any type can be catalysed.
In order to obtain the resultant products at a sufficiently high yield and reasonable reaction rates, it is advantageous if not only the relative reactivity of the reacting electrophilic compounds towards the nucleophilic compounds but also the nucleophilicity N of the nucleophilic compounds used do not fall below certain minimum values.
The parameter N for the nucleophilicity of a compound was introduced by Mayr and Patz, Angew. Chem. 1994, 106, 990-1010.
For numerous nucleophilic compounds, the value N can be taken from this publication, in particular pages 1003-1004. Table 1 also contains a number of N values.
The relative reactivity of electrophilic compounds can be specified, inter alia, by using the ethanolysis rate constant kEtOH, i.e. the solvolysis rate constant in 100% ethanol at 25xc2x0 C.
This fundamental quantity can be used in particular for specifying the relative reactivity of alkyl halides, in particular alkyl chlorides or alkyl bromides. The corresponding values for kEtOH (25xc2x0 C.) for numerous alkyl halides can be taken from, for example, the publication by J. P. Dau-Schmidt and H. Mayr in Chem. Ber. 1994, 127, pages 205-212, or the dissertation by J. P. Dau-Schmidt, Lxc3xcbeck Medical University 1992.
Alkyl halides which are suitable here for a reaction of alkyl halides, in particular alkyl chlorides or alkyl bromides, induced by the lithium salt according to formula (1) in a suspension in non-coordinating organic solvents, preferably in dichloromethane, are those having a kEtOH (25xc2x0 C.) value of xe2x89xa75xc3x9710xe2x88x925sxe2x88x921, or by the lithium salt according to formula (1) in a xe2x89xa70.03 molar solution in coordinating organic solvents, preferably in diethyl ether, are alkyl halides, in particular alkyl chlorides or alkyl bromides, having kEtOHxe2x89xa71xc3x9710xe2x88x923sxe2x88x921.
When the magnesium salt according to formula (1) is used suspended in non-coordinating organic solvents, preferably in dichloromethane, it is advantageous to use alkyl halides, in particular chlorides or bromides, having a kEtOH (25xc2x0 C.) value of xe2x89xa71xc3x9710xe2x88x927 sxe2x88x921.
The corresponding nucleophilic compounds reacting with the alkyl halides should in all cases have a value N of xe2x89xa71.62.
Examples of alkyl halides, preferably alkyl chlorides or alkyl bromides, having the specified minimum values kEtOH, but which do not represent an exhaustive listing, are alkyl halides where alkyl is preferably unbranched or branched C1-C10-alkyl which is unsubstituted or substituted at the a carbon atom by 1 to 3 identical or different radicals of any type, in particular by aryl, preferably C6-C10-aryl, substituted aryl, for example methoxyphenyl, tolyl, cumenyl, aminophenyl, di- or trialkylaminophenyl, C2-C6-alkenyl, for example 1-methyl-2-butenyl, C5-C6-cycloalkenyl, in particular cyclopentenyl, and 1,1-dimethyl-2-butynyl, 3-pentan-2-yl. Halide is fluoride, chloride, bromide or iodide, preferably chloride and bromide, particularly preferably chloride.
Hereinafter is set forth a tabulation (1.1.) of selected alkyl chlorides which can be used as possible reaction partners of allyltrimethylsilane or more reactive nucleophiles (Nxe2x89xa71.62) in a suspension of LiC(SO2CF3)3 in dichloromethane: 
In accordance with the above reaction diagram (1.2), alkyl chlorides having an ethanolysis rate constant kEtoHxe2x89xa75xc3x9710xe2x88x925 sxe2x88x921 give well-stabilized carbocations with the Li salts of the formula (1) used according to the invention and are therefore suitable for the reaction with nucleophilic compounds having a value Nxe2x89xa71.62.
Selected alkyl chlorides which, in a 0.03 M solution of LiC(SO2CF3)3 in diethyl ether can be used as possible reaction partners of allyltrimethylsilane or more reactive nucleophiles (Nxe2x89xa71.62) may be taken from the tabulation (1.3) below: 
In accordance with the reaction diagram (1.4), alkyl chlorides with an ethanolysis rate constant kEtOH (25xc2x0 C.)xe2x89xa71xc3x9710xe2x88x921, sal give, with the Li salts of the formula (1) used according to the invention, well-stabilized carbocations which can be reacted with nucleophilic compounds having Nxe2x89xa71.62.
Selected alkyl chlorides which, in a suspension of Mg(C(SO2CF3)3)2 in dichloromethane, can be used as possible reaction partners of allyltrimethylsilane or more reactive nucleophiles (Nxe2x89xa71.62) may be taken from the tabulation (1.5) below: 
In accordance with the above reaction diagram (1.6), alkyl chlorides having an ethanolysis rate constant kEtOH (25xc2x0 C.)xe2x89xa71xc3x9710xe2x88x927 sxe2x88x921 give, with the Mg salts of the formula (1) used according to the invention, well-stabilized carbocations which react well with nucleophilic compounds having Nxe2x89xa71.62.
The relative reactivity of an electrophilic compound towards a nucleophilic compound in the reaction induced according to the invention can also be made by specifying the relative reactivity constant krel. Krel describes, for example, the relative reactivities of acetals and alkyl ethers towards allyltrimethylsilane in dichloromethane in the presence of catalytic amounts of ZnCl2 etherate. Corresponding values can be taken from H. Mayr, J.-P. Dau-Schmidt, Chem. Ber. 1994, 127, 213-217.
Suitable compounds for the reactions induced according to the invention by the lithium salt of formula (1) suspended in non-coordinating solvents, preferably in dichloromethane, as catalyst, are preferably acetals or alkyl ethers, preferably methyl ether, whose relative reactivity constant krei is greater than or equal to that of benzaldehyde dimethylacetal. When the magnesium salt according to formula (1) is used, the acetals or alkyl ethers, preferably methyl ether, should have a relative reactivity constant krel which is greater than or equal to that of 1-tolyl-1-methoxyethane, where the nucleophilic compound should have a value Nxe2x89xa71.62 in all cases.
Dialkylacetals of any ketones or aldehydes, in particular C1-C6-alkylacetals, particularly preferably dimethylacetals, mixed and cyclic dialkylacetals, can be used provided that they have the specified relative reactivity constant krel. This also applies to alkyl ethers of any hydroxyl compounds, where alkyl is preferably C1-C6-alkyl, in particular methyl or ethyl, or to N,O-acetals, i.e. to reaction products of any disubstituted amines, for example diisopropylamine or ethylphenylamine, with alcohols and aldehydes, in particular formaldehyde.
The tabulation (1.7) below sets forth selected methyl ethers and acetals which can be used as possible reaction partners of allyltrimethylsilane or more reactive nucleophiles (Nxe2x89xa71.62) in a suspension of LiC(SO2CF3)3 in dichloromethane. 
According to the above reaction diagram (1.8), reactions of acetals or methyl ethers whose relative reactivity constant krel xe2x89xa7 that of benzaldehyde dimethylacetal are possible.
The tabulation (1.9) below presents selected methyl ethers and acetals which can be used as possible reaction partners of allyltrimethylsilane or more reactive nucleophiles (Nxe2x89xa71.62) in a suspension of Mg(C(SO2CF3)3)2 in dichloromethane. 
According to the above reaction diagram (1.10), methyl ethers or acetals can be reacted with nucleophiles having Nxe2x89xa71.62 provided that their relative reactivity constant kdrel is greater than or equal to that of 1-tolyl-1-methoxyethane.
In the tabulations above, the abbreviations have the following meanings:
An 4-methoxyphenyl radical
Ph phenyl radical
Tol 4-methylphenyl radical
Me methyl radical
The Lewis acid catalysts used according to the invention can also induce reactions of aldehydes whose reactivity is greater than or equal to that of benzaldehyde towards nucleophiles having a nucleophilicity Nxe2x89xa75, for example towards 1-phenyl-1-trimethylsiloxyethene, 1-trimethylsiloxycyclopentene or 1-methoxy-1-trimethylsiloxy-2-methyl-1-propene. Suitable aldehydes are in particular benzaldehyde or methoxybenzaldehyde. Preferably, suspensions of Li salts or Mg salts of the formula (1) are used as Lewis acid catalysts for this.
Preferably, this Lewis acid catalyst system is also used for inducing the reaction of ketones having a reactivity greater or equal to that of acetophenone towards nucleophiles having a nucleophilicity Nxe2x89xa79, for example methoxy-1-trimethylsiloxy-2-methyl-1-propene.
Preference is also given to th e use of Li salts or Mg salts of the formula (1) as Lewis acid catalysts, preferably without addition of a solvent, for catalysing the reaction of carbonyl halides, in particular carbonyl chlorides or carbonyl bromides, whose reactivity is greater than or equal to that of benzoyl chloride towards nucleophiles having a nucleophilicity Nxe2x89xa79, for example 1-methoxy-2-methyl-1-trimethylsiloxypropane.
This also applies to the reaction of carboxylic anhydrides whose reactivity is greater than or equal to that of acetic anhydride towards nucleophiles having a nucleophilicity Nxe2x89xa7xe2x88x922.
Li salts and Mg salts of the formula (1) also induce the [4+2]-cycloaddition of any dienes, for example 2,3-dimethyl-1,3-butadiene or cyclopentadiene. The olefins to be reacted with the dienes preferably bear electron-withdrawing substituents. Examples are methyl vinyl ketone or maleic anhydride. The cycloadditions generally proceed even at room temperature and are significantly accelerated in comparison with the uncatalysed reactions, generally by a factor of about 1.5. As an additional effect, the formation of the endo product is preferred. For [4+2] cycloadditions, the use of compounds of the formula (1) as a suspension in dichloromethane is preferred, where the concentration is 2-20 mol %, preferably 5-15 mol %, based on the dienophile to be activated.
The reactions are generally carried out at a temperature of from 0 to 60xc2x0 C., preferably at from 10 to 30xc2x0 C., under inert gas.
Preferably, tris(trifluoromethylsulfonyl)methane is suitable in a concentration of 0.5-10 mol %, preferably 1-5 mol %, based on the electrophilic acyl halide, preferably acyl chloride, for example acetyl chloride or benzoyl chloride, for the catalysis of Friedel Crafts acylations. Preferentially, the reaction temperatures of 60-105xc2x0 C., preferably 80-110xc2x0 C., should be maintained here.
This also applies to a corresponding intramolecular Friedel-Crafts acylation.
The reaction times are generally 2 to 250 hours, preferably from 3 to 72 hours, and particularly preferably from 12 to 48 hours.
The starting materials, electrophile and nucleophile, are used either as solution in the solvent or suspension medium of the catalyst compound of the formula (1), for example diethyl ether or dichloromethane, or, if they are liquid at the reaction temperature, as solvent-free substance.
The solvents or suspension media used for the reactions according to the invention are in each case anhydrous; they are dehydrated in a known manner.
The course of the reaction can be followed in each case by GC or HPLC.
After the reaction is completed, the reaction mixture is worked up in a customary manner, for example by hydrolysis with water and extraction with use of coordinating solvent or else by filtering off with use of non-coordinating solvent. The crude product can be purified, for example by chromatography, recrystallization or distillation.
The compound of the formula (1) is recovered either by filtering off the reaction mixture or by evaporating the aqueous phase produced after the hydrolysis of the reaction mixture. The compound (1) thus recovered can be purified in a customary manner, for example by suspension in a suitable solvent, for example dichloromethane/pentane (1/1 v/v) and subsequent filtration with suction. The compound is then dried in a conventional manner to constant weight, for example at 120-170xc2x0 C./0.01 to 0.1 mbar, before it is reused.
Other reaction parameters must be taken from the general protocols for homogeneous or heterogeneous syntheses which are induced using the novel catalysts of the formula (1), in which case these instructions can be applied to all compounds of the formula (1) being used according to the invention in corresponding homogeneous or heterogeneous synthesis.
The invention further relates to the Mg compound of the formula (1) used according to the invention.
This Mg tris[(trifluoromethyl)sulfonyl]methanide can be obtained by reacting magnesium carbonate with tris(trifluoromethyl)sulfonyl)methane, preferably in stoichiometric amounts. As solubilizer, water was added until slight gas evolution started and the solids passed into solution. A highly viscous colourless solution was obtained. From this solution, the Mg salt of the formula (1) can be produced by drying. Since the salt is highly hygroscopic, it must be kept under protective gas.